A human stomach cell type transcriptome atlas.

BACKGROUND: The identification of cell type-specific genes and their modification under different conditions is central to our understanding of human health and disease. The stomach, a hollow organ in the upper gastrointestinal tract, provides an acidic environment that contributes to microbial defence and facilitates the activity of secreted digestive enzymes to process food and nutrients into chyme. In contrast to other sections of the gastrointestinal tract, detailed descriptions of cell type gene enrichment profiles in the stomach are absent from the major single-cell sequencing-based atlases. RESULTS: Here, we use an integrative correlation analysis method to predict human stomach cell type transcriptome signatures using unfractionated stomach RNAseq data from 359 individuals. We profile parietal, chief, gastric mucous, gastric enteroendocrine, mitotic, endothelial, fibroblast, macrophage, neutrophil, T-cell, and plasma cells, identifying over 1600 cell type-enriched genes. CONCLUSIONS: We uncover the cell type expression profile of several non-coding genes strongly associated with the progression of gastric cancer and, using a sex-based subset analysis, uncover a panel of male-only chief cell-enriched genes. This study provides a roadmap to further understand human stomach biology.

Knowledge gaps and confidence in counseling about aneuploidy screening and testing: A survey of prenatal care clinicians.

OBJECTIVES: Comprehensive counseling on prenatal genetic screening and diagnostic testing is challenging for clinicians. We sought to identify baseline clinician knowledge of prenatal genetic screening and diagnostic testing and needs to promote counseling aligned with ACOG recommendations. METHODS: We performed an anonymous, cross-sectional survey of clinicians at two unaffiliated, tertiary academic institutions to assess the knowledge of, confidence in, and time spent counseling on prenatal genetic screening and diagnostic testing. Stata (Version 17, College Station, TX) was used to perform descriptive statistics. Deductive and inductive coding was used to analyze responses regarding ideal education resources. RESULTS: The survey response rate was 78% (100/129). Only 36% of respondents correctly answered knowledge questions about prenatal genetic screening and diagnostic testing. A majority, 59% (16/39), of those confident or extremely confident in counseling were unable to answer all questions accurately. Respondents reported a median of 5.6 min (95% CI 4.9-6.4 min) spent counseling. Thematic analysis of free responses revealed desire for visual tools that discuss financial costs and patient values. CONCLUSIONS: Surveyed clinicians demonstrated deficiencies in knowledge about prenatal genetic counseling. To provide better and more comprehensive care, we noted a desire for the development of formalized resources for clinician and patient education.

Lung cancer associated with cystic airspaces.

OBJECTIVE: The objectives of this study were to determine the frequency of lung cancers associated with a discrete cystic airspace and to characterize the morphologic and pathologic features of the cancer and the cystic airspace. MATERIALS AND METHODS: We reviewed all diagnosed cases of lung cancer resulting from baseline screening (n=595) and annual screening (n=111) in the International Early Lung Cancer Action Program to identify those abutting or in the wall of a cystic airspace. We also reviewed the pathologic specimens. RESULTS: A total of 26 lung cancers were identified abutting or in the wall of a cystic airspace. Of these, 13 were identified at baseline (13/595, 2%) and 13 at annual screening (13/111, 12%), which was significant (p<0.0001). The median circumferential portion of wall involved was less for the annual cancers than for the baseline ones, but this difference did not reach significance (90° vs 240°, p=0.07). The diagnosis was adenocarcinoma in all but three cases. Histologic analysis showed that the cystic space was a bulla, a fibrous walled cyst without a defined lining, or a pleural bleb and that in all but one case, the tumor was eccentric relative to the airspace and the wall of the airspace was unevenly thickened. CONCLUSION: At annual repeat CT screening, the finding of an isolated cystic airspace with increased wall thickness should raise the suspicion of lung cancer.

Sequelae of cryotherapy in breast tissue.

Cryotherapy is a novel treatment for benign and malignant breast lesions that is under evaluation. We assessed the acute and subacute outcomes of breast cryotherapy in normal goat teats using physical, microscopic, and imaging modalities. Eight goats were subjected to two freeze-thaw cycles of breast tissue producing a 2cm iceball and sacrificed either 2 or 7 weeks later. Acute skin changes were minimal unless obvious tissue injury occurred during cryotherapy; however, depigmentation developed over several weeks in dark-skinned goats despite the presence of melanocytes. By histology, breast epithelial elements could not be identified at cryotherapy sites. There was no cystic degeneration, which is common at surgical excision sites. Neither calcifications nor prominent scarring could be attributed to cryotherapy on imaging studies after 2 or 7 weeks. When compared to standard breast surgery, the sequelae of cryotherapy using histologic, radiographic, and sonographic criteria were decreased. Our study suggests that cryotherapy, with technical modifications, is feasible within breast tissue and warrants further study.

Pharmacokinetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT.

Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to investigate the pharmacokinetics, pharmacodynamics and the safety of melagatran therapy at three different doses. Steady-state plasma concentrations were rapidly achieved and maintained throughout the infusion period. The mean plasma concentrations in the low, medium and high dose groups were 0.17, 0.31 and 0.53 micromol/l, respectively. The prolongation of APTT was stable during the melagatran infusions and correlated to the plasma concentration. Phlebographically verified regression of thrombus size measured as decrease in Marder score was seen after 4 to 6 days in 8 of 12 patients, 6 of 12 patients and 5 of 11 patients in the low, medium and high dose groups of melagatran and in 5 of the heparin-treated patients. In the low dose group with melagatran, thrombus extension was seen in one patient. At the dose levels studied, melagatran was well tolerated with no clinically significant bleeding problems, suggesting that melagatran could safely be given to patients suffering from DVT.

Acute renal failure in pregnancy.

Acute renal failure (ARF) during pregnancy is a rare event. However, the care of the woman diagnosed with ARF is a challenge for the perinatal care team. The physiologic hydronephrosis and hydroureter of pregnancy alters clinical parameters for assessing the woman diagnosed with ARF. Urinary stasis and enhanced filtration predisposes to alterations in 24-hour urine evaluations, increased urinary creatinine excretion, and lower BUN and serum creatinine values. If the renal system becomes compromised, the woman is at risk for acidemia, fluid and electrolyte imbalances, and pregnancy compromise. The perinatal nurse must have an understanding of normal pregnancy physiology and an appreciation for how pregnancy physiology may alter renal assessments. Furthermore, the nurse must know the impact that ARF can have on maternal status and fetal well-being. Astute, continuous assessments of maternal and fetal status are required to detect subtle changes. While maternal status is the primary concern, it must not be forgotten that a change in fetal status may be the first indication of underlying maternal compromise.

[Aortic traumatic lesion. Has tomodensitometry a role?]. / Lésion traumatique aortique. La tomodensitométrie a-t-elle un rôle?

The low positive yield from aortography in patients with suspected traumatic aortic rupture has prompted research into CT of the mediastinum as a screening investigation which could significantly reduce the number of negative angiograms performed. Much of the data published to date suggest a promising role for CT, but false negative scans have been reported and the precise false negative rate has yet to be determined. We propose an algorithm for the use of CT in suspected traumatic rupture but emphasise that continuous monitoring of outcomes and further large studies are required before CT can become an established screening technique.

Periportal halo: a CT sign of liver disease.

Periportal halos are defined as circumferential zones of decreased attenuation identified around the peripheral or subsegmental portal venous branches on contrast-enhanced computed tomography (CT). These halos probably represent fluid or dilated lymphatics in the loose areolar zone around the portal triad structures. While this CT finding is nonspecific, it is abnormal and should prompt close scrutiny of the liver in search of an underlying etiology. Periportal halos which may be due to blood are commonly seen in patients with liver trauma. Periportal edema may cause this sign in patients with congestive heart failure and secondary liver congesion, hepatitis, or enlarged lymph nodes and tumors in the porta hepatis which obstruct lymphatic drainage. This CT sign has also been observed in liver transplants (probably secondary to disruption and engorgement of lymphatic channels) and in recipients of bone marrow transplants who might develop liver edema from microvenous occlusive disease. While the precise pathophysiologic basis of periportal tracking has not been proven, it represents a potentially important CT sign of occult liver disease.

Imaging of regional spread of breast cancer by internal mammary lymphoscintigraphy, CT, and MRI.

Forty women with breast cancer underwent imaging by internal mammary lymphoscintigraphy (IMLS), which was correlated with the results of CT and MRI of the chest. IMLS was performed and interpreted using the previously described methods of Ege. It identified 22 instances of ipsilateral internal mammary nodal involvement, none of which corresponded to cases of abnormally enlarged (diameter greater than 1.0 cm) internal mammary nodes on CT and/or MRI. Positive IMLS was associated with axillary nodal metastases in 15 out of 22 instances. The authors conclude that IMLS provides information on regional nodal spread of breast cancer that is not available with either CT/MRI imaging or axillary biopsy.

Computed tomography in the evaluation of the aorta in patients sustaining blunt chest trauma.

Computed tomography is used with increasing frequency to evaluate blunt chest trauma. Since traumatic aortic rupture (TAR) is a rapidly lethal condition, unnecessary CT scanning may not be justified. To determine the accuracy of chest CT scanning for TAR, we reviewed 17 patients who underwent both chest CT scanning and aortography. Five patients had TAR by aortography. CT scanning yielded three true positives and two false negatives. In 12 patients with a negative aortogram, CT scanning recorded four false positives and eight true negatives. The specificity was 23% and the sensitivity was 83% compared with aortography. The overall accuracy for CT scanning was 53%. From these data we conclude that in the presence of an unstable patient or where there is a strong clinical suspicion of TAR the patient should proceed directly to aortography.

CT and MR imaging of partial anomalous pulmonary venous return to the azygos vein.

Partial anomalous pulmonary venous return to the azygos vein is very unusual, occurring in 0.02% of autopsy examinations. We report the CT, magnetic resonance, and angiographic findings in a 67-year-old man with partial anomalous venous return to the azygos vein.

Diagnosis of ectopic pregnancy: endovaginal vs transabdominal sonography.

During a 25-month period, 193 women with the clinical diagnosis of suspected ectopic pregnancy had transabdominal and endovaginal sonograms. Most had quantitative determinations of serum human chorionic gonadotropin (HCG). Endovaginal sonography was diagnostic of ectopic pregnancy in 23 (38%) of the 60 patients with surgically proved ectopic pregnancies: transabdominal sonography was diagnostic in 13 patients (22%). All 83 intrauterine pregnancies were identified with endovaginal sonography, compared with 34 identified with transabdominal sonography. Endovaginal sonography was somewhat more helpful in the diagnosis of missed abortion and blighted ovum. Eighty endovaginal sonograms were classified as indeterminate as compared with 141 transabdominal studies. This indeterminate group included patients with complete abortions, ectopic pregnancies without sonographic evidence of an extrauterine gestation, incomplete abortions, and patients with subsequent negative serum levels. As in prior reports, endovaginal sonography was superior to transabdominal sonography in the evaluation of suspected ectopic pregnancies. Overall, endovaginal sonography was diagnostic in 113 patients, whereas transabdominal sonography was diagnostic in 52 patients. The finding of an extrauterine fetal pole or embryo was diagnostic for an ectopic pregnancy. Pelvic fluid, the appearance of the endometrium, and a single positive serum HCG determination were not helpful in making the diagnosis of ectopic pregnancy.

Prospective comparison of radionuclide, computed tomographic, sonographic, and magnetic resonance localization of parathyroid tumors.

The appropriate choice of imaging techniques to localize parathyroid tumors preoperatively remains controversial. We report the first prospective, blinded study to compare the efficacy of four imaging modalities in 100 patients with primary hyperparathyroidism (pHPT). Patients were examined by computer-assisted thallium 201/technetium 99m subtraction scintigraphy (TTS), computed tomography (CT), ultrasonography (US), and magnetic resonance (MR). Each study was performed and interpreted independently. Subsequent neck exploration and "curative" parathyroidectomy allowed correlation of surgical findings with imaging reports to score their accuracy. Overall sensitivities of the four imaging modalities were TTS, 73%, CT, 68%, US, 55%; and MR, 57%; with respective specificities of 94%, 92%, 95%, and 87%. Sensitivities for lesions located below the thyroid gland (thymic tongue and mediastinum) were TTS, 90%; CT, 46%; US, 44%; and MR, 50%; with respective specificities of 100%, 99%, 100%, and 94%. There was a significant increase in overall sensitivity when TTS and CT (90%, p less than 0.01) or TTS and US (85%, p less than 0.05) were used together; however, the combination of any three or even four imaging modalities did not increase sensitivity further. For small parathyroid tumors (less than or equal to 250 mg), no imaging technique had a sensitivity of more than 50%. None of the imaging studies accurately localized small hyperplastic parathyroid glands found in patients with multiple gland disease. Preoperative parathyroid imaging may not be indicated in pHPT patients undergoing first-time neck exploration because surgeons experienced in parathyroid surgery have a 93% to 96% cure rate.

Dose to the cardiac vascular and conduction systems in primary breast irradiation.

Using computerized tomography (CT) in which cardiac anatomy was defined, doses delivered to the cardiac compartments, vascular and conduction systems were assessed for various standard techniques of primary breast irradiation. Included in the analysis were 6 MV photon tangents (T) alone, or in conjunction with a separate internal mammary field (IMF). Beams evaluated in the IMF were 6 MV photons, 12 MeV electron beam, and mixed photon/electron beam; Cobalt 60 was also analyzed as an alternate photon beam. Treatment of the IMF with photons, either alone or in combination with electron beam, delivered doses ranging between 30 Gy to 50 Gy to all chambers of the heart, coronary arteries and branches of the conduction system. Complete sparing of the posterior cardiac structures and volume is accomplished with treatment plans using tangents alone or in combination with 12 MeV electron beam irradiation to the IMF. Sparing of the anterior wall of the left ventricle, Bundle of His and left anterior descending coronary artery is also achieved in treatment with tangents and 12 MeV electron beam IMF. Doses to this region with tangents alone ranged from 20 Gy to 45 Gy compared to 0 to 30 Gy with tangents and 12 MeV electron beam IMF. Clinical significance of these findings will be discussed.

Inability of sonography to detect imminent ovulation.

Sonographic visualization of the cumulus oophorus or of morphologic alterations in the wall of the dominant follicle have been reported to be reliable signs of imminent ovulation when conventional transabdominal sonography is used. To determine if transvaginal sonography could allow a more frequent and confident prediction of imminent ovulation, we prospectively monitored 22 ovulatory menstrual cycles in four women undergoing artificial insemination and in 13 normally menstruating volunteers. Scanning was done on alternate days in the periovulatory period; a 7.5-MHz transvaginal transducer was used. Despite the improved resolution obtained with transvaginal sonography, confident identification of the cumulus oophorus or of mural changes in the follicle was not possible in any of the cycles followed. No other consistent follicular characteristic predicted imminent ovulation. We conclude that confident prediction of imminent ovulation is not possible with sonographic analysis.

Computed tomography of pulmonary thromboembolism and infarction.

Computed tomographic findings in 18 patients with pulmonary thromboembolism are retrospectively reviewed. In the majority of patients, thromboembolism was not suspected clinically. The CT findings can be divided into two groups: vascular and parenchymal changes. The most frequent vascular findings is an intraluminal filling defect or defects due to thrombus. The most frequent parenchymal finding is a triangular (wedge-shaped) pleural-based soft tissue attenuation lesion. Although CT is not a primary diagnostic tool in the evaluation of pulmonary thromboembolism, CT may be helpful in diagnosis of pulmonary embolism, when evaluating an undiagnosed parenchymal density.

CT evaluation of parathyroid adenomas: diagnostic criteria and pitfalls.

Sixty-three patients with biochemically proven primary hyperparathyroidism underwent CT of the neck and upper chest prior to surgery. All examinations were prospectively evaluated. Parathyroid adenomas were correctly identified on CT in 81% of patients. Thyroid adenomas, tortuous vessels, the esophagus, and atypical parathyroid adenomas may be potential sources of error in the diagnosis of parathyroid adenomas.